| Summary: | Acute Lymphoblastic Leukaemia (ALL) is the most common leukaemia in childhood (Hemminki and Jiang 2002), and Neuroblastoma (NB) is the most common extracranial solid tumour (Eng 2008). Here, transcriptome sequencing has been used to screen for novel point mutations and fusion genes in four paediatric ALLs, three primary neuroblastomas, and 1 cell line (IMR32). A total of 9,648 Mb of sequence was generated using both lIIumina and FLX platforms. In ALL, a (G-7A) substitution in exon 14 of the mitochondrial membrane protein SAMM50 gene was identified, however sequencing of the SAMM50 coding region in a further 47 ALLs did not uncover additional mutations. In one neuroblastoma sample a fusion transcript between GATC and COX6A1 was recovered and shown to be due to an ~18.9Kb germline microduplication spanning two genes including the p53 interacting inhibitor of apoptosis, TRIAP1 (Park and Nakamura 2005). This gene maps to 12q24.31, a prognostically important region of common gain in NB (Mosse et al 2007, Wolf et al 2010) and TRIAP1 expression was found to be high in stage 4 neuroblastoma and associated with poor prognosis in multiple datasets, highlighting its potential relevance to 12q24.31 gain. Finally, across all samples a total of 205 transcripts with rearranged exon order relative to genomic structure were identified (referred to here as posttranscriptional exon shuffling events or PTES). Although these were subsequently found to be abundantly expressed in a wide variety of normal tissues, PTES transcripts from MAN1A2, TLE4 and CDK13 were found to be both highly expressed relative to other isoforms, and conserved in mice. This is the first genome wide experimental analysis of such transcripts, and suggests that some could be of functional importance.
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